Abstract: Absence epilepsy is a non-convulsive generalized seizure disorder characterized by a sudden arrest of consciousness and 3-5Hz spike-and-wave discharges (SWDs) in electroencephalography (EEG) recordings (Crunelli and Leresche, 2002). Absence seizure generation involves reciprocal circuitry between neurons of the thalamus and cortex. Voluntary hyperventilation reliably triggers SWDs in the EEG of absence patients and, therefore, is used to clinically diagnose this childhood form of epilepsy (Penry and Dreifuss, 1969; Adams and Leuders, 1981). The mechanism(s) fully elucidating how induced-hyperventilation precipitates SWDs remains unknown, despite the knowledge of such a link for over four decades (North et al., 1990; Wirrell et al., 1981). Many studies demonstrate that hyperventilation and the associated change in brain pH modulate neuronal excitability (Dulla et al., 2005) and epileptic activity (Miley, and Forster, 1977). Neurons sensitive to brain pH are known as central respiratory chemoreceptors (Guyenet et al., 2010). Collectively, these neurons modulate their activity through pH-sensitive ion channels and G-protein coupled receptors (GPCRs) (Guyenet et al., 2010). Two GPCRs, OGR1 and GPR4, are proposed to mediate neuronal activity in the brain (Schneider et al., 2012; Huang et al., 2007). We set out to determine whether hyperventilation alters SWDs in the EEG of two rodent models of absence epilepsy: the DBA/2J mouse and the WAG/Rij rat. To do so, we pharmacologically induced hyperventilation in vivo (Cotten, 2013) and measured ensuing SWD activity. Preliminary data from these experiments indicates that SWD frequency and duration increases following i.p. injection in both our rodent models compared to vehicle injection. Our preliminary EEG studies motivated our hypothesis that pH-sensitive neurons in the thalamus trigger hyperventilation-induced SWDs. To begin testing this hypothesis, we first set out to characterize the level of expression of OGR1 and GPR4 in the thalamus. We used multi-label fluorescence in situ hybridization to assess expression. Our data shows that GPR4, but not OGR1, mRNA is abundant in the thalamus. Moreover, GPR4 mRNA is localized to excitatory (VGLUT2+) cells within the thalamus. Our future experiments will assess how these putative pH-sensitive neurons are modulated by hyperventilation-induced changes in brain pH.